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Developmental biology - Epigenetics|
Environment Affects Father's Genes & His Kids Genes
An international research team led by ETH [Swiss Federal Institute of Technology in Zurich] Professor Christian Wolfrum, has now shown that one key variable in the formation of brown adipose tissue is determined before conception. Males who spend time in low temperatures prior to mating will produce offspring with more active brown adipose tissue. This quite literally means that the environmental impact a father experiences is passed on to his offspring.
The work is published in the journal Nature Medicine, 9 July 2018.
Analysing computed tomography images
The researchers reached this conclusion by studying mice, but in humans too, there is a correlation between the ambient temperature before conception and the increase in brown fat. Together with colleagues at the University Hospital Zurich, the ETH scientists analysed computed tomography images of 8,400 adult patients. They noted that people born between July and November (meaning they were conceived in the colder half of the year) have significantly more active brown adipose tissue than people born between January and June (who were conceived in the hotter half of the year).
To follow up on this correlation, the researchers conducted studies in mice. They kept the animals at either a moderate (23° Celsius) or a cool (8° Celsius) temperature before allowing them to mate. An analysis of their offspring showed that the temperature females were kept at before and after mating had no impact on levels of brown adipose tissue in their offspring. However, males kept in a cool environment for several days prior to mating had more active brown adipose tissue than those of males kept in a temperate environment. In addition, the offspring of these males were better protected against excess weight - gaining less weight on a high-fat diet - and against metabolic disorders.
Epigenetic changes in sperm
Researchers used data from in vitro fertilisation and other studies on sperm, to demonstrate the information about a father's ambient temperature is passed on to his offspring via his sperm's epigenetic programming. This refers to changes made in the methylation pattern of his DNA.
It was known for several years that certain environmental factors can modify the epigenetic pattern of sperm. What scientists now show for the first time is that ambient temperature can also lead to epigenetic changes.
Temperatures at home and excess weight
The results that ETH scientists obtained from their studies of mice and men agree with earlier observations that people in cold regions have particularly high levels of brown adipose tissue. "Until now, the assumption was that this had something to do with the temperatures people experienced during their lifetime," Wolfrum says, "but our observations suggest that temperatures prior to conception might also affect later levels of brown fat."
He points out another correlation, average indoor temperatures have increased in recent decades. In the United States, research corroborates this finding. What's more, studies show that the temperature people experience at home correlates with how overweight they are. "Our work highlights a possible mechanism explaining this," he adds.
Does this mean couples trying for children should be advised to have the man go for a swim in a cold lake or even play about in the snow before having relations? Wolfrum :"Before we can give that kind of advice, we need to study the correlation in people more closely, but, it is likely that the exposure to cold needs to persist over a longer period for it to have an effect on epigenetic programming. Taking a plunge in cold water or spending a short time lying on a block of ice probably won't be enough." His team is now planning a study that will compare the epigenetic programming of human sperm in summer and winter.
Recent research has focused on environmental effects that control tissue functionality and systemic metabolism. However, whether such stimuli affect human thermogenesis and body mass index (BMI) has not been explored. Here we show retrospectively that the presence of brown adipose tissue (BAT) and the season of conception are linked to BMI in humans. In mice, we demonstrate that cold exposure (CE) of males, but not females, before mating results in improved systemic metabolism and protection from diet-induced obesity of the male offspring. Integrated analyses of the DNA methylome and RNA sequencing of the sperm from male mice revealed several clusters of co-regulated differentially methylated regions (DMRs) and differentially expressed genes (DEGs), suggesting that the improved metabolic health of the offspring was due to enhanced BAT formation and increased neurogenesis. The conclusions are supported by cell-autonomous studies in the offspring that demonstrate an enhanced capacity to form mature active brown adipocytes, improved neuronal density and more norepinephrine release in BAT in response to cold stimulation. Taken together, our results indicate that in humans and in mice, seasonal or experimental CE induces an epigenetic programming of the sperm such that the offspring harbor hyperactive BAT and an improved adaptation to overnutrition and hypothermia.
Authors: Wenfei Sun, Hua Dong, Anton S. Becker, Dianne H. Dapito, Salvatore Modica, Gerald Grandl, Lennart Opitz, Vissarion Efthymiou, Leon G. Straub, Gitalee Sarker, Miroslav Balaz, Lucia Balazova, Aliki Perdikari, Elke Kiehlmann, Sara Bacanovic, Caroline Zellweger, Daria Peleg-Raibstein, Pawel Pelczar, Wolf Reik, Irene A. Burger, Ferdinand von Meyenn and Christian Wolfrum.
We are grateful to M. Stoffel, J. Krützfeldt and members of the Wolfrum lab for helpful discussions, K. Tabbada for assistance with WGBS high-throughput sequencing, and F. Krueger and S. Andrews for help with bioinformatics analysis. We thank K. De Bock and F. Zheng for the IB4 antibody and K. A. Rollins for editing the manuscript. Data produced and analyzed in this paper were generated in collaboration with the Genetic Diversity Center (GDC) and Functional Genomics Center Zurich (FGCZ). The work was supported by the Swiss National Science Foundation (SNSF; C.W. and F.v.M.).
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Research results indicate that in humans as well as in mice, seasonal temperature induces an epigenetic response in sperm that is passed onto offspring and perhaps is retained in the genome - the complete set
of genes or genetic material present in a cell or organism - as an improved adaptation to hypothermia.
Image: Science Direct.